US 12,600,766 B2 · Anti-TDP-43 binding molecules and uses thereof

Abstract

The present invention is in the field of transactive response DNA binding protein with a molecular weight of 43 kDa (TARDB or also TDP-43). The invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or an antigen-binding fragment or a derivative thereof and uses thereof. The present invention provides means and methods to diagnose, prevent, alleviate and/or treat a disease, disorder and/or abnormality associated with TDP-43 aggregates including but not limited to Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Chronic Traumatic Encelopathy (CTE), and limbic-predominant age-related TDP-43 encephalopathy (LATE).

A TDP-43 binding molecule, which binds misfolded aggregated TDP-43 and non-aggregated physiological TDP-43 and which comprises:

a) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
11;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
12;
and VH-CDR3 comprising the amino acid sequence ES (Glu-Ser);
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
15;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
16;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
17;
or
b) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
21;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
22;
and VH-CDR3 comprising the amino acid sequence ES (Glu-Ser);
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
25;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
16;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
27;
or
c) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
31;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
32;
and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:
33;
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
35;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
36;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
37;
or
d) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
41;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
42;
and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:
43;
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
45;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
46;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
47;
or
e) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
61;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
62;
and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:
63;
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
65;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
66;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
67;
or
f) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
71;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
72;
and VH-CDR3 comprising the amino acid sequence 73;
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
75;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
16;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
77;
or
g) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
81;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
82;
and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:
83;
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
85;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
86;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
87;
or
h) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
101;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
102;
and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:
103;
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
105;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
106;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
107;
or
i) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
121;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
122;
and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:
123;
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
125;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
16;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
127;
or
j) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
141;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
142;
and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:
143;
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
145;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
146;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
147;
or
k) VH-CDR1 comprising the amino acid sequence of SEQ ID NO:
151;
VH-CDR2 comprising the amino acid sequence of SEQ ID NO:
152;
and VH-CDR3 comprising the amino acid sequence of SEQ ID NO:
153;
VL-CDR1 comprising the amino acid sequence of SEQ ID NO:
155;
VL-CDR2 comprising the amino acid sequence of SEQ ID NO:
156;
and VL-CDR3 comprising the amino acid sequence of SEQ ID NO:
157;
or a humanized antibody or an antigen-binding fragment thereof.

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Anti-TDP-43 binding molecules and uses thereof

Life of this patent

Anti-TDP-43 binding molecules and uses thereof

Life of this patent

Abstract

Claims15